1,25-Dihydroxyvitamin D3-Conditioned CD11c+Dendritic Cells are Effective Initiators of CNS Autoimmune Disease

被引:18
作者
Besusso, Dario [1 ,2 ,3 ]
Saul, Louise [1 ,2 ,3 ]
Leech, Melanie D. [1 ,2 ,3 ]
O'Connor, Richard A. [1 ,2 ,3 ]
MacDonald, Andrew S. [4 ]
Anderton, Stephen M. [1 ,2 ,3 ]
Mellanby, Richard J. [1 ,2 ,3 ,5 ]
机构
[1] Univ Edinburgh, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland
[2] Univ Edinburgh, Ctr Multiple Sclerosis Res, Edinburgh, Midlothian, Scotland
[3] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland
[4] Univ Manchester, Manchester Collaborat Ctr Inflammat Res, Manchester, Lancs, England
[5] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin Inst, Edinburgh EH9 1QH, Midlothian, Scotland
来源
FRONTIERS IN IMMUNOLOGY | 2015年 / 6卷
基金
英国惠康基金;
关键词
dendritic cell; vitamin D; experimental autoimmune encephalomyelitis; multiple sclerosis; T cell; TOLEROGENIC DENDRITIC CELLS; VITAMIN-D-RECEPTOR; REGULATORY T-CELLS; 1-ALPHA; 25-DIHYDROXYVITAMIN D-3; SELF-ANTIGEN; IN-VITRO; ENCEPHALOMYELITIS; INDUCTION; DIFFERENTIATION; ACTIVATION;
D O I
10.3389/fimmu.2015.00575
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DC) play a crucial role in regulating T cell activation. Due to their capacity to shape the immune response, tolerogenic DC have been used to treat autoimmune diseases. In this study, we examined whether 1,25 dihydroxyvitamin D-3-conditioned bone marrow-derived DC (VitD-BMDC) were able to limit the development of autoimmune pathology in experimental autoimmune encephalomyelitis (EAE). We found that VitD-BMDC had lower expression of MHC class II and co-stimulatory molecules and were less effective at priming autoreactive T cells in vitro. Using our recently described BMDC-driven model of EAE, we demonstrated that VitD-BMDC had a significantly reduced ability to initiate EAE. We found that the impaired ability of VitD-BMDC to initiate EAE was not due to T cell tolerization. Instead, we discovered that the addition of 1,25(OH)(2)D-3 to BMDC cultures resulted in a significant reduction in the proportion of CD11c+ cells. Purified CD11c+ VitD-BMDC were significantly less effective at priming T cells in vitro yet were similarly capable of initiating EAE as vehicle-treated CD11c+ BMDC. This study demonstrates that in vitro assays of DC function can be a poor predictor of in vivo behavior and that CD11c+ VitD-BMDC are highly effective initiators of an autopathogenic T cell response.
引用
收藏
页码:1 / 11
页数:11
相关论文
共 49 条
  • [21] GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c+MHCII+ Macrophages and Dendritic Cells
    Helft, Julie
    Boettcher, Jan
    Chakravarty, Probir
    Zelenay, Santiago
    Huotari, Jatta
    Schraml, Barbara U.
    Goubau, Delphine
    Reis e Sousa, Caetano
    [J]. IMMUNITY, 2015, 42 (06) : 1197 - 1211
  • [22] Tolerogenic dendritic cell therapy for rheumatoid arthritis: where are we now?
    Hilkens, C. M. U.
    Isaacs, J. D.
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2013, 172 (02) : 148 - 157
  • [23] Biologic agents in rheumatology: unmet issues after 200 trials and $200 billion sales
    Ioannidis, John P. A.
    Karassa, Fotini B.
    Druyts, Eric
    Thorlund, Kristian
    Mills, Edward J.
    [J]. NATURE REVIEWS RHEUMATOLOGY, 2013, 9 (11) : 665 - 673
  • [24] Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring
    Kappos, Ludwig
    Bates, David
    Edan, Gilles
    Eraksoy, Mefkure
    Garcia-Merino, Antonio
    Grigoriadis, Nikolaos
    Hartung, Hans-Peter
    Havrdova, Eva
    Hillert, Jan
    Hohlfeld, Reinhard
    Kremenchutzky, Marcelo
    Lyon-Caen, Olivier
    Miller, Ariel
    Pozzilli, Carlo
    Ravnborg, Mads
    Saida, Takahiko
    Sindic, Christian
    Vass, Karl
    Clifford, David B.
    Hauser, Stephen
    Major, Eugene O.
    O'Connor, Paul W.
    Weiner, Howard L.
    Clanet, Michel
    Gold, Ralf
    Hirsch, Hans H.
    Radue, Ernst-Wilhelm
    Sorensen, Per Soelberg
    King, John
    [J]. LANCET NEUROLOGY, 2011, 10 (08) : 745 - 758
  • [25] 1,25-DIHYDROXYVITAMIN-D3 PREVENTS THE INVIVO INDUCTION OF MURINE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
    LEMIRE, JM
    ARCHER, DC
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (03) : 1103 - 1107
  • [26] LOW AVIDITY RECOGNITION OF SELF-ANTIGEN BY T-CELLS PERMITS ESCAPE FROM CENTRAL TOLERANCE
    LIU, GY
    FAIRCHILD, PJ
    SMITH, RM
    PROWLE, JR
    KIOUSSIS, D
    WRAITH, DC
    [J]. IMMUNITY, 1995, 3 (04) : 407 - 415
  • [27] Cutting edge: Th2 response induction by dendritic cells: A role for CD40
    MacDonald, AS
    Straw, AD
    Dalton, NM
    Pearce, EJ
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 168 (02) : 537 - 540
  • [28] The vitamin D receptor is necessary for 1α,25-dihydroxyvitamin D3 to suppress experimental autoimmune encephalomyelitis in mice
    Meehan, TF
    DeLuca, HF
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2002, 408 (02) : 200 - 204
  • [29] TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis
    Mellanby, Richard J.
    Cambrook, Helen
    Turner, Darryl G.
    O'Connor, Richard A.
    Leech, Melanie D.
    Kurschus, Florian C.
    MacDonald, Andrew S.
    Arnold, Bernd
    Anderton, Stephen M.
    [J]. JOURNAL OF NEUROINFLAMMATION, 2012, 9
  • [30] Role of regulatory T-cells in autoimmunity
    Mellanby, Richard J.
    Thomas, David C.
    Lamb, Jonathan
    [J]. CLINICAL SCIENCE, 2009, 116 (7-8) : 639 - 649